Transport mechanisms of 3-[I-123]Iodo-alpha-methyl-L-tyrosine in a human glioma cell line: Comparison with [H-3-methyl]-L-methionine

The amino acid analog 3-[I-123]iodo-oc-methyl-L-tyrosine (IMT) is under cli nical evaluation as a SPECT tracer of amino acid transport in brain tumors. This study investigated the carrier systems involved in IMT transport in h uman glioma cells in comparison with [H-3-methyl]-L-methionine (H-3-MET). M ethods: Human glioma cells, type 86HG-39, were cultured and incubated for 1 min at 37 degrees C with IMT and H-3-MET in the lag phase (1.2 d after see ding), exponential growth phase (3 d after seeding), and plateau phase (8 d after seeding). Experiments were performed in the presence and absence of Na+, during inhibition of system L amino acid transport by 2-aminobicyclo[2 .2.1]heptane-e-carboxylic acid (BCH), and during inhibition of system A ami no acid transport by 2-(methylamino)-isobutyric acid (MeAIB). Results: IMT and H-3-MET uptake decreased by 55%-73% when the cells entered from the exp onential growth phase into the plateau phase (P < 0.05; n = 3-11). Inhibiti on by BCH reduced uptake of IMT in the lag phase, exponential growth phase, and plateau phase by 90%-98% (P < 0.001; n = 3-6) and the uptake of H-3-ME T by 73%-83% (P < 0.001; n = 3-11). In a Na+-free medium H-3-MET uptake was reduced by 23%-33% (P < 0.05; n = 3-11), whereas IMT uptake was not signif icantly different. MeAIB showed no significant effect on IMT or H-3-MET upt ake in either phase. Conclusion: Transport of both IMT and H-3-MET depends on the proliferation rate of human glioma cells in vitro and is dominated b y BCH-sensitive transport. These data indicate that system L is induced in rapidly proliferating glioma cells and is the main contributor to the uptak e of both tracers. H-3-MET transport showed a minor Na+ dependency that was not attributable to system A. The similarity of transport mechanisms of bo th tracers emphasizes the clinical equivalence of IMT SPECT and C-11-MET PE T for the diagnostic evaluation of gliomas.